The discovery of antibiotics has been one of the greatest achievements of modern medicine. However, antibiotic resistance is recognized as a major problem worldwide in the management of infectious disease, both in hospital settings and in the community. However, wound infection due to multidrug resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA) continues to increase.
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of infection in injured patients, and healthcare associated (HA) and community associated (CA) MRSA have become prevalent in recent years. Its emergence is a consequence of excessive use of certain antibiotics. MRSA generally does not cause infection in the absence of injury. When MRSA enters the body through a cut or abrasion, it may cause infection by evading the natural protective mechanisms of the body. This necessitates the use of alternative therapies, which ideally do not result in resistance through continuous selective pressure. MRSA infections in recent years have been treated with mupirocin, clindamycin, trimethoprim/sulfamethoxazole, doxycycline, minocycline, linezolid, vancomycin, daptomycin, and telavancin [Bjorn et al., Anti-infectious and anti-inflammatory effects of peptide fragments sequentially derived from the antimicrobial peptide centrocin 1 isolated from the green sea urchin, Strongylocentrotus droebachiensis. AMB Express 2012, 2:67]. Also, vancomycin, linezolid, daptomycin (Cubicin), tigecycline (Tygacil), and telavancin (Vibativ) were reported to treat severe MRSA infections of skin and soft tissue in hospitals. Vancomycin, the primary treatment for MRSA, possessed high minimum inhibitory concentration (MIC) values and other limitations [Palazzolo-Ballance et al., Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. J Immunol 2008, 180:500-9].
Cationic gene-encoded host defense peptides (HDP) are nature's most diverse and lavish class of antibiotics. A subclass of HDP, known as antimicrobial peptides (AMP), exerts direct antimicrobial activity. Antimicrobial peptides (AMPs) are part of the host defense system of a wide range of invertebrates, plants, and animals [Lee et al., A helix-PXXP-helix peptide with antibacterial activity without cytotoxicity against MDRPA-infected mice. Biomaterials. 2014; 35:1025-1039; Wimley & Hristova, Antimicrobial peptides: successes, challenges and unanswered questions. The Journal of membrane biology. 2011; 239:27-34]. AMPs typically show potent antimicrobial activity against a broad range of bacteria, virus, fungi, and protozoans. The key features of AMPs are that they are short, amphipathic, and cationic, they possess rapid killing ability, and they target the membrane and internal components of the cell [Brogden, Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria, Nature reviews Microbiology. 2005; 3:238-250; Yount & Yeaman, Immunocontinuum: perspectives in antimicrobial peptide mechanisms of action and resistance. Protein and peptide letters. 2005; 12:49-67; Yeaman & Yount, Mechanisms of antimicrobial peptide action and resistance. Pharmacological reviews. 2003; 55:27-55; Hancock & Scott, The role of antimicrobial peptides in animal defenses. Proceedings of the National Academy of Sciences of the United States of America. 2000; 97:8856-8861].
Piscidin AMPs were found to be made up of 21˜44 residues and possess an amphipathic-helical structure [Maisetta et al., In Vitro Bactericidal Activity of Human β-Defensin 3 against Multidrug-Resistant Nosocomial Strains. Antimicrobial Agents and Chemotherapy 2006; 50:806-809; Winkler et al., Unexpected Challenges in Treating 432 Multidrug-resistant Gram-negative Rods: Resistance to Ceftazidime-Avibactam in Archived Isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2014]. In 2012, five new piscidins, named tilapia piscidins 1˜5 (TP1˜5), were isolated from Nile tilapia (Oreochromis niloticus) [Peng et al., Five Different Piscidins from Nile Tilapia, Oreochromis niloticus: Analysis of Their Expressions and Biological Functions. PloS ONE 2012; 7(11): e50263].
However, there is still a need to develop a new therapy or new therapeutics for wound healing, particular for treating MRSA infections in wounds.